TWI750737B - Use of bio-transformed bear bile powder in preparation of medicines for treating lps-induced pulmonary inflammation - Google Patents

Abstract

A use of bio-transformed bear bile powder in preparation of medicines for treating lps-induced pulmonary inflammation is disclosed. The present invention carries out a comparative research on the anti-inflammatory drug activity of bio-transformed bear bile powder and natural bear bile powder. A research is made on the effect of the bio-transformed bear bile powder and natural bear bile powder on carrageenan-induced rat inflammation models, and a research is made on the effect of the bio-transformed bear bile powder on LPS-induced lung inflammation in mice. Experimental results show that the bio-transformed bear bile powder administration group obviously reduces plantar swelling of carrageenan-induced inflammation model in rats, and the effect thereof is not lower than that of the natural bear bile powder. Both the bio-transformed bear bile powder and the natural bear bile powder can significantly reduce levels of the inflammatory factors IL-6 and TNF-α in the lung and the serum. It is therefore that the bio-transformed bear bile powder can be used to prepare the anti-inflammatory drugs.

Description

Application of biotransformed bear bile powder in the preparation of drugs for the treatment of LPS-induced pulmonary inflammation use

The present invention relates to the field of pharmacy. More specifically, it particularly relates to the application of biotransformed bear bile powder in the preparation of a medicine for treating LPS-induced pulmonary inflammation.

Bear bile, which is obtained by drying the gallbladder bile of the bear family black bear or brown bear, has the functions of clearing heat, calming the liver and improving eyesight. Bear bile is one of the four precious animal medicines, with a history of more than 2,000 years, and a large number of prescriptions contain bear bile ingredients. The annual output of bear bile powder in my country is about 30 tons, which still cannot meet the needs of human health. At present, the increasingly prominent contradiction between supply and demand of high-end bear bile powder and the continuous increase in the market demand for bear bile powder for low-end raw materials have made the price of bear bile powder continue to rise, and the market price has exceeded 5,000 yuan/kg. What is even more serious is that the long-term resistance of domestic and foreign animal protection organizations to the extraction of live bear bile, especially the recent "Guizhentang" incident has once again attracted extensive attention from the international and domestic society, and has given rise to the production of domestic bear bile powder and the development of related industries. brought unprecedented resistance. Therefore, accelerating the research and development of artificial bear bile is the key to promoting the sustainable development of the bear bile industry.

The application number is 201410588581.5 (authorized announcement number CN104382941B), and the Chinese patent named as an artificial bear bile powder and a preparation method thereof provides an artificial bear bile powder and a preparation method thereof. Animal bile simulates biocatalytic transformation in vitro, and artificial bear bile is made through a certain process, but there is no use of this artificial bear bile powder for the preparation of medicines. Research.

In order to solve the problems in the prior art, the present invention provides the application of biotransformed bear bile powder in the preparation of a medicine for treating LPS-induced pulmonary inflammation.

In order to achieve the above object, the present invention adopts the following technical solutions: learn from the patent of Authorized Announcement No. CN104382941B, the biotransformation bear bile powder is prepared by the following method: a) using the buffer solution of pH=7～9 for the poultry bile powder After dissolving, centrifuge under 11000g conditions for 10min, filter repeatedly to obtain filter residue and filtrate, and freeze-dry the filter residue for preservation; the poultry gallbladder powder is fenugreek gall powder, duck gallbladder powder, goose gallbladder powder, ox gallbladder powder, One or more mixtures of rabbit bile powder, dog bile powder and sheep bile powder, the main components and mass percentages are as follows: total bile acid: 40~65%, amino acid: 4~9%, trace element: 0.5~1%, Wherein, the total cholic acid contains TCDCA (sodium taurochenodeoxycholate), and the mass percentage of the TCDCA in the poultry bile powder is 40-50%; b) adding the filtrate into the filtrate containing 7α-hydroxyl The reaction is carried out in a reactor of steroid dehydrogenase, 7β-hydroxysteroid dehydrogenase and coenzyme I or coenzyme II; the 7α-hydroxysteroid dehydrogenase, 7β-hydroxysteroid dehydrogenase are immobilized in the reactor c) The reaction solution after the reaction is freeze-dried for 48 hours and mixed with the filter residue to obtain the biotransformed bear bile powder.

The first aspect of the present invention provides the application of biotransformed bear bile powder in the preparation of anti-inflammatory drugs.

In another preferred embodiment, the anti-inflammatory drugs include the biotransformed bear bile powder and pharmaceutical acceptable excipients.

In another preferred embodiment, the dosage form of the anti-inflammatory drug is an oral dosage form or a non-oral dosage form.

In another preferred embodiment, the oral dosage form is tablet, powder, granule, capsule, emulsion, syrup or spray.

In another preferred example, the parenteral dosage form is an injection or an external preparation.

In another preferred embodiment, the external preparation is eye drops.

In another preferred embodiment, the biotransformed bear bile powder is an artificial bear bile powder prepared from poultry bile as a raw material through biological fermentation.

In another preferred example, the poultry bile is extracted from one or more of fenugreek bile powder, duck bile powder, goose bile powder, ox bile powder, rabbit bile powder, dog bile powder, sheep bile powder, preferably For the bile powder.

The second aspect of the present invention provides the application of the biotransformed bear bile powder in the preparation of anti-pneumonia drugs.

In another preferred embodiment, the anti-pneumonia drug includes the biotransformed bear bile powder and pharmaceutically acceptable excipients.

In another preferred embodiment, the dosage form of the anti-pneumonic drug is an oral dosage form or a non-oral dosage form.

In another preferred embodiment, the oral dosage form is tablet, powder, granule, capsule, emulsion, syrup or spray.

In another preferred example, the parenteral dosage form is an injection or an external preparation.

In another preferred embodiment, the external preparation is eye drops.

In another preferred example, the biotransformed bear bile powder is made of poultry bile as a raw material. Artificial bear bile powder prepared by biological fermentation.

In another preferred example, the poultry bile is extracted from one or more of fenugreek bile powder, duck bile powder, goose bile powder, ox bile powder, rabbit bile powder, dog bile powder, sheep bile powder, preferably For the bile powder.

The present invention adopts the above-mentioned technical scheme, and compared with the prior art, has the following technical effects: the present invention has carried out a comparative study on the pharmacodynamic activity of treating LPS-induced pulmonary inflammation to biotransformed bear bile powder and natural bear bile powder, and Animal experiments on the effect of biotransformed bear bile powder on rat inflammation model, and research on the effect of biotransformed bear bile powder on LPS-induced lung inflammation in mice. The experimental results show that the anti-inflammatory effect of biotransformed bear bile powder is no less than that of natural bears bile powder, thus revealing the broad prospect of biotransformed bear bile powder in the preparation of anti-inflammatory drugs.

It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described in the following (eg, the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, we will not repeat them one by one.

Fig. 1 is a graph showing the effect of biotransformed bear bile powder on the swelling degree of carrageenan-induced rat inflammatory model in Example 1; Fig. 2 is a graph showing the effect of natural bear bile powder on carrageenan-induced rat in Example 1. Figure 3 shows the effect of inflammatory factor IL-6 in the serum of LPS-induced mouse lung inflammation after continuous administration of bear bile powder for 7 days in Example 2; Figure 4 is Example 2 The effect of continuous administration of bear bile powder for 7 days on the inflammatory factor IL-6 in the bronchoalveolar lavage fluid of mice with LPS-induced lung inflammation; Figure 5 shows the effect of continuous administration of bear bile powder for 7 days in Example 2 on the inflammatory factor TNF-α in the serum of LPS-induced mouse lung inflammation; Figure 6 shows the effect of continuous administration of bear bile powder for 7 days in Example 2 on the The influence of inflammatory factor TNF-α in the bronchoalveolar lavage fluid of mice with lung inflammation induced by LPS; Fig. 7 is the HE staining microscope picture of lung tissue under 20 times objective lens in Example 2, A is the control group, B is the model group, and I Be the natural bear bile powder 1000mg/kg group, J is the biotransformation bear bile powder 1000mg/kg group; Fig. 8 is the lung tissue damage evaluation statistics chart in the embodiment 2, A is the control group, B is the model group, and I is the natural Bear bile powder 1000mg/kg group, J is the biotransformation bear bile powder 1000mg/kg group.

The biotransformation bear bile powder is prepared by using the bile powder, and the specific steps are as follows:

The first step is to prepare the bile powder: the bile is purchased from the slaughterhouse, and the quantity and weight of the bile are first determined; the local part of the bile is sterilized with 75% alcohol, and then the bile is dissected separately; The bile was freeze-dried for 48 hours to obtain bile powder, which was stored in a desiccator for later use.

The second step, the treatment of the bile powder: use the buffer solution with pH=7.0~9.0 to dissolve the bile powder, prepare a 1L solution, fully dissolve it with ultrasonic waves to obtain the bile powder solution, and centrifuge the bile powder solution at 11000g for 10 minutes. , filtered several times, and the supernatant (filtrate) was stored at 4°C as a treatment solution of poultry gall powder for later use; the filter residue was freeze-dried and stored for later use.

Wherein, the buffer is one of phosphate buffered saline (PBS), Tris-HCl buffer (tris-hydroxymethylaminomethane) or glycine-sodium hydroxide buffer (Gly-NaOH).

The third step, preparation of immobilized enzyme: chitosan (water-soluble) with a mass fraction of 1% Add an appropriate amount of acetic acid to the solution, and magnetically stir for 30 minutes to obtain a chitosan acetic acid solution. The above solution is injected into 100 mL of a 3% sodium tripolyphosphate solution by a high-pressure syringe pump to solidify for 1 to 2 hours to obtain uniform particle size and regular shape. The white chitosan spheres were then filtered and washed several times with deionized water. Put the prepared chitosan spheres into a beaker with a mass fraction of 0.125% glutaraldehyde aqueous solution, and place them in a shaker at 37°C under 170 g, and activate them for 2 to 4 hours to obtain activated chitosan microspheres. .

Weigh 10g of the above activated chitosan microspheres, load them into a small chromatography column, add an appropriate amount of 7α-hydroxysteroid dehydrogenase and 7β-hydroxysteroid dehydrogenase, and combine them by vertical mixing for 4-6 hours, and the fixation is completed. , release the enzyme solution, and rinse the fixed enzyme column with PBS buffer 3 to 5 times. The immobilization rate of 7α-hydroxysteroid dehydrogenase and 7β-hydroxysteroid dehydrogenase is greater than 90%.

Wherein, the 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH) are derived from microorganisms, such as Clostridium sardiniense (DSM599/ATCC27555), Pseudomonas fragilis Bacteroides fragilis ATCC25825 or Collinsella aerofaciens ATCC25986.

The fourth step, biocatalytic conversion: adding the prepared poultry and animal bile powder treatment solution to the above-mentioned immobilized enzyme column as a reaction substrate solution, adding coenzyme I or coenzyme II, so that coenzyme I (or coenzyme II): TCDCA=1 : 2~1:4 (molar ratio), at 20~30℃, react for 2~6h.

The fifth step, the treatment of the reaction solution: the reaction solution after the fourth step is freeze-dried for 48h to obtain a solid reaction product, and finally the filter residue obtained in the second step is mixed with the above-mentioned solid reaction product. Gall powder.

The above-mentioned biotransformed bear bile powder can be used in the preparation of anti-inflammatory drugs.

In another preferred embodiment, the anti-inflammatory drug includes the biotransformed bear bile powder and pharmaceutically acceptable excipients.

In another preferred example, the dosage form of the anti-inflammatory drug is an oral dosage form or a non-oral dosage form.

In another preferred example, the oral dosage form is tablet, powder, granule, capsule, emulsion, syrup or spray.

In another preferred example, the parenteral dosage form is an injection or an external preparation.

In another preferred example, the external preparation is eye drops.

In another preferred example, the biotransformed bear bile powder is an artificial bear bile powder prepared from poultry bile as a raw material through biological fermentation.

In another preferred example, the poultry bile is extracted from one or more of fenugreek bile powder, duck bile powder, goose bile powder, ox bile powder, rabbit bile powder, dog bile powder, sheep bile powder, preferably For the bile powder.

The above-mentioned biotransformed bear bile powder can be used in the preparation of anti-pneumonia drugs.

In another preferred embodiment, the anti-pneumonia drug includes the biotransformed bear bile powder and pharmaceutically acceptable excipients.

In another preferred embodiment, the dosage form of the anti-pneumonic drug is an oral dosage form or a non-oral dosage form.

In another preferred example, the oral dosage form is tablet, powder, granule, capsule, emulsion, syrup or spray.

In another preferred example, the parenteral dosage form is an injection or an external preparation.

In another preferred example, the external preparation is eye drops.

In another preferred example, the biotransformed bear bile powder is an artificial bear bile powder prepared from poultry bile as a raw material through biological fermentation.

In another preferred example, the poultry bile is extracted from fenugreek bile powder, duck bile powder, goose bile powder, One or more of ox gallbladder powder, rabbit gallbladder powder, dog gallbladder powder and sheep gallbladder powder, preferably ox gallbladder powder.

The present invention will be described in detail and concretely below through specific embodiments, so as to make the present invention better understood, but the following embodiments do not limit the scope of the present invention.

Example 1

Biotransformed bear bile powder and natural bear bile powder were used to study carrageenan-induced inflammation in rats. The experiments are as follows:

Animal species: 6-week-old male SD rats, weight range at receipt: 132-199g, weight range at administration: 152-225g, SD rats are from Hunan Slike Jingda Laboratory Animal Co., Ltd., and the grade is SPF , Laboratory animal production license number: SCXK (Xiang) 2016-0002 (valid until September 29, 2021), issued by the Hunan Provincial Department of Science and Technology, laboratory animal quality certification number: 43004700060779.

Animal grouping method: After the quarantine, the qualified rats were selected and randomly divided into 9 groups according to their body weight, namely the negative control group (10 rats/group), the model group (10 rats/group), and the biotransformed bear bile powder low Dose group, middle-dose group, high-dose group (10 animals/group), natural bear bile powder low-dose group, medium-dose group, high-dose group (10 animals/group), and positive control group (10 animals/group).

Negative control substance and solvent: The negative control substance is 0.5% mass fraction of sodium carboxymethyl cellulose solution (CMC-Na) (analytical grade), the specification is 500g/bottle, the batch number is 20150806, and the manufacturer is Tianjin Damao Chemical Reagent factory, there is no special temperature and humidity limit during preparation, weigh CMC-Na, add ultrapure water to dissolve, prepare a solution with a concentration of 0.5% CMC-Na by mass fraction, store at room temperature, without humidity limit; the storage period is 7 days. Solvent: The test substance and positive control drug were prepared with 0.5% sodium carboxymethyl cellulose solution (CMC-Na) (analytical grade).

Dose and group design of the experiment: The experiment consists of 9 groups, namely: negative control group (blank pair control group), model group, biotransformed bear bile powder low-dose group, middle-dose group, high-dose group, natural bear bile powder low-dose group, middle-dose group, high-dose group, positive control group (indomethacin group) , 10 animals per group, male, see Table 1 for details.

In Table 1, each group was given 10 mL/kg, and the negative control group and model group were given 0.5% CMC-Na solution.

The administration route, administration frequency and administration period of the test substance and reference substance in the experiment: all were administered by gavage, and the administration volume was 10 mL/kg. After the quarantine was over, the animals were divided into groups, and each group was administered once. .

Description of the test method: The qualified SD rats were selected and randomly divided into 9 groups, namely the negative control group, the model group, the biotransformed bear bile low-dose group, the middle-dose group, the high-dose group, and the natural bear bile powder low-dose group. , middle-dose group, high-dose group, and positive control indomethacin group, with 10 animals in each group, all male. Before modeling, each animal was marked with a line at the ankle joint of the right hind foot, and the volume of the right hind foot was measured with a plantar volume meter, which was measured twice in a row, and the average value was taken as the base volume. Except for the blank control group, the animals in the other groups were injected with a mass fraction of 1% carrageenan suspension under the fascia of the palmar tendon of the right hind foot, 0.1 mL per animal; the animals in the blank control group were injected with an equal volume of normal saline; The corresponding drugs were given by gavage immediately after carrageenan. At 1h, 2h, 3h, 4h, 5h, and 6h after injection, the plantar volume of the right hind foot of the animals in each group was measured. 2 consecutive measurements were taken, and the average value was taken as the foot plantar volume after modeling. According to the volume of the plantar at different time points after the inflammation, the swelling degree and swelling inhibition rate of the plantar were calculated.

Swelling inhibition rate (%)=(average swelling degree of model group-average swelling degree of administration group)/average swelling degree of model group×100%

Statistical analysis method of the test: All data were entered into EXCEL for statistical analysis. In different groups, the mean ± standard deviation of the swelling degree of the foot was calculated. SPSS software was used to test the normal distribution of the data between the groups, and one-way variance was used. Analysis The differences between groups were compared, and the data were tested for homogeneity of variance before the comparison. When the variances between groups were homogeneous, LSD, Bonferroni and SNK tests were used for statistical analysis; when the variances between groups were not homogeneous, Dunnett's T3 test was used. , Dunnett's C test for statistical analysis, the test results are shown in Table 2-3, and Figure 1-2.

In Table 2, compared with the negative control group, # indicates p<0.05; compared with the model group, * indicates p<=0.05.

It can be seen from the experimental results that compared with the negative control group, the swelling degree of the soles of the feet in the model group was significantly increased (p<0.01), indicating that carrageenan had successfully induced inflammation and the modeling was successful. Compared with the model group, the swelling degree of the feet of the animals in the biotransformed bear bile powder 0.093g/kg, 0.185g/kg groups and the natural bear bile powder 0.09g/kg, 0.18g/kg groups were reduced (p<0.05 or p<0.05). 0.01), and the biotransformed bear bile powder has a more obvious effect on reducing the swelling of the soles of the feet. It showed that the biotransformed bear bile powder group had better anti-inflammatory effect on carrageenan-induced inflammation model animals than the natural bear bile powder.

It can be seen that the pharmacodynamic activity of biotransformed bear bile powder in inflammation is comparable to that of natural bear bile powder, indicating that biotransformed bear bile powder can be used to prepare anti-inflammatory drugs and has better pharmacodynamic activity.

Example 2

Biotransformed bear bile powder and natural bear bile powder were used to study the effects of LPS-induced lung inflammation in mice. The experiments are as follows:

Animal germline: 45 male C57BL/6 mice, from Shanghai Lingchang Biotechnology Co., Ltd., experimental animal production license number: SCXK (Shanghai) 2013-0018.

Dose and group design of the experiment: A total of 4 groups were set up, namely blank control group, LPS model control group, biotransformed bear bile powder 1000 mg/kg group, and natural bear bile powder 1000 mg/kg group.

Description of the test method: The mice in the LPS model control group and each administration group were exposed to aerosolized LPS (2.5 mg/ml) twice a day (30 minutes each time, 2 hours apart) for 7 consecutive days. After the second nebulization every day, mice in each group were given different test drugs. 5 hours after the end of the second nebulization on days 1, 4 and 7 of the experiment, orbital blood was collected and placed in a centrifuge tube. After standing at room temperature for 2 hours, the serum was separated by centrifugation at 2000g for 20 minutes, frozen at -80°C for later use, and the levels of IL-6 and TNF-α in the serum were detected. After blood collection on the 7th day of the experiment, the thoracic cavity of the mice was opened. The left lung lobe of the mouse was ligated, and the trachea was intubated, and washed three times with 0.5 ml of PBS each time, and the recovered solution was collected and placed in a centrifuge tube. Centrifuge at 4°C, 1500 rpm for 10 minutes, take the supernatant, freeze it at -80°C, and detect the levels of IL-6 and TNF-α in bronchoalveolar lavage fluid. The lung tissue on the ligated side was taken and fixed in formalin solution. Lung specimens from 5 mice in each group were randomly selected for histopathological examination after sectioning and HE staining.

2.1 The effect of biotransformed bear bile powder on the inflammatory factor IL-6 in serum and bronchoalveolar lavage fluid of LPS-induced mouse lung inflammation, as shown in Table 4 and Figures 3-4. Among them, Figure 3 shows the effect of continuous administration of bear bile powder for 7 days on the inflammatory factor IL-6 in the serum of LPS-induced mice lung inflammation, and Figure 4 shows the effect of continuous administration of bear bile powder for 7 days on LPS-induced lung inflammation in mice Influence of inflammatory factor IL-6 in bronchoalveolar lavage fluid.

Note: Compared with the model control group, * means P<0.05, ** means P<0.01

It can be seen from Table 4 and Figures 3-4: C57BL/6 mice were exposed to aerosolized LPS to induce lung inflammation, and each group of mice were given natural bear bile powder 1000mg/kg and biotransformed bear bile powder 1000mg/kg by gavage respectively. kg, the IL-6 level in the serum of the mice detected on the 1st and 4th days was not significantly different from that of the model control group. Continuous administration to the 7th day, the levels of IL-6 in the serum of mice in the natural bear bile powder 1000mg/kg group and the biotransformation bear bile powder 1000mg/kg group were significantly lower than those in the model control group (P<0.05 or P<0.05). <0.01). In the natural bear bile powder 1000mg/kg group and the biotransformation bear bile powder 1000mg/kg group, the level of IL-6 in the bronchoalveolar lavage fluid of mice on the 7th day was significantly lower than that of the model control group (P<0.05 or P<0.05 or P<0.05). 0.01).

2.2 The effect of biotransformed bear bile powder on the inflammatory factor TNF-α in serum and bronchoalveolar lavage fluid of mice with LPS-induced lung inflammation The results are shown in Table 5 and Figures 5-6.

Among them, Figure 5 shows the effect of continuous administration of bear bile powder for 7 days on the inflammatory factor TNF-α in serum of LPS-induced mouse lung inflammation; Figure 6 shows the effect of continuous administration of bear bile powder for 7 days on LPS-induced mouse lung Influence of inflammatory factor TNF-α in bronchoalveolar lavage fluid of external inflammation.

Note: Compared with the model control group, * means P<0.05, ** means P<0.01

It can be seen from Table 5 and Figures 5-6 that: C57/BL6 mice were exposed to aerosolized LPS to induce lung inflammation, and the levels of inflammatory factor TNF-α in serum and bronchoalveolar lavage fluid of mice in each group were detected. Day 1 and 4 mice There was no significant difference in serum TNF-α level compared with the model control group. Continuous administration to the 7th day, the natural bear bile powder 1000mg/kg group and the biotransformation bear bile powder 1000mg/kg group, the level of TNF-α in the serum of the mice on the 7th day was significantly lower than that of the model control group (P <0.05 or P<0.01). When biotransformed bear bile powder 1000mg/kg was given by gavage, the concentration of TNF-α in the bronchoalveolar lavage fluid of mice on the 7th day was lower than that of the model control group (P>0.05); natural bear bile powder 1000mg was given by gavage /kg, the concentration of TNF-α in the bronchoalveolar lavage fluid of mice on the 7th day was significantly lower than that of the model control group (P<0.05).

The experimental results showed that the LPS-induced C57/BL6 mouse model was given bear bile powder and biotransformed bear bile powder, respectively, which could significantly reduce the levels of inflammatory factors IL-6 and TNF-α in the lungs and serum, indicating that bear bile powder and The biotransformed bear bile powder has a certain anti-inflammatory effect, indicating that the biotransformed bear bile powder can be used for the preparation of anti-inflammatory drugs and has better pharmacodynamic activity.

2.3 The effect of biotransformed bear bile powder on the pathological changes of LPS-induced lung inflammation in mice.

As shown in Figure 7-8, under the 20x objective lens, the alveolar septa in the blank control group were thin and rarely infiltrated by inflammatory cells (Figure 7A). In the model group, the alveolar septa were thickened and the alveolar cavities disappeared, similar to fibrosis. Massive accumulation of inflammatory cells was seen around the bronchi and small blood vessels (Fig. 7B).

The following scoring criteria were used to score the lung injury in each group of mice:

No damage to alveolar structures within the visual field—0

Structural damage in 0-25% field of view—1

Structural damage in 25%-50% field of view—2

Structural damage in 25%-50% of the field of view──3

Diffuse injury—4

After administration of biotransformed bear bile powder and natural bear bile powder, natural bear bile powder 1000mg/kg (Fig. 8I) and biotransformation bear bile powder 1000mg/kg (Fig. 8J) treated the pathological changes of lung inflammation in mice The effect is remarkable. The results showed that both natural bear bile powder and biotransformed bear bile powder had a certain improvement effect on LPS-induced lung injury in mice.

The specific embodiments of the present invention have been described above in detail, but they are only used as examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions to the present invention are also within the scope of the present invention. Therefore, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be included within the scope of the present invention.

Claims (7)

The application of a biotransformed bear bile powder in the preparation of a medicine for treating LPS-induced pulmonary inflammation. Application of the biotransformed bear bile powder according to claim 1 of the above-mentioned patent application in the preparation of a medicine for treating LPS-induced pulmonary inflammation, wherein the medicine for treating LPS-induced pulmonary inflammation includes the biotransformed bear bile powder and pharmaceutically acceptable excipients. Application of the biotransformed bear bile powder according to claim 1 of the above-mentioned application for the preparation of a medicine for the treatment of LPS-induced pulmonary inflammation, wherein the dosage form of the medicine for the treatment of LPS-induced pulmonary inflammation is an oral dosage form or parenteral dosage forms. Application of the biotransformed bear bile powder described in claim 3 of the above-mentioned patent application in the preparation of a medicine for the treatment of LPS-induced pulmonary inflammation, wherein the oral administration forms are tablets, powders, granules, capsules, Emulsion, syrup or spray. The application of the biotransformed bear bile powder described in claim 3 of the above-mentioned patent scope in the preparation of an anti-pneumonic drug, wherein the non-oral dosage forms are injections and external preparations. Application of the biotransformed bear bile powder described in claim 1 of the above-mentioned patent application in the preparation of a medicine for the treatment of LPS-induced pulmonary inflammation, wherein the biotransformed bear bile powder is based on poultry bile as a raw material, and undergoes a biological fermentation route. The prepared artificial bear bile powder. Application of the biotransformed bear bile powder described in claim 6 of the above-mentioned patent application in the preparation of a medicine for the treatment of LPS-induced pulmonary inflammation, wherein the poultry bile is extracted from bile powder, duck bile powder, goose bile powder, One or more of ox bile powder, rabbit bile powder, dog bile powder and sheep bile powder.

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